In Vivo Therapeutic Potential of Next-Generation Probiotic Akkermansia muciniphila and Butyrate Combination Therapy in Diabetes

Abstract

Recent studies have found that gut microbiota is closely related to the initiation and progression of T1DM. This study aimed to examine the effects of sodium butyrate and Akkermansia muciniphila (AKK), both individually and combined, on T1DM models. To optimize a T1DM model, a single high dose of streptozotocin (STZ) was administered to C57BL/6J mice to determine the appropriate dose (150 mg/kg). Mice were divided into four groups: a control group, a diabetic group, a diabetic group treated with butyrate, and a diabetic group treated with AKK. The groups treated with butyrate and AKK reduced blood glucose levels, prevented body weight loss, and normalized food and water intake. To explore the synergistic effects of AKK and butyric acid, Sprague-Dawley (SD) rats were assigned to control, diabetic, and treatment groups including butyrate, AKK, and combination therapy. Two weeks of oral treatment showed improved metabolic parameters in the treatment groups. The combination therapy exhibited the most improvements. In the in vitro experiment, the cytotoxic effects of STZ on 3T3-L1 cells treated with both AKK and butyric acid were measured, indicating their protective effects on cell viability. GC-MS/MS analysis was also performed to assess changes and correlations in systemic short-chain fatty acids (SCFAs). SCFAs were significantly increased in the liver after probiotic treatment, especially in the combination therapy group. These findings demonstrate the microbiota-regulating and therapeutic effects of AKK and butyrate, particularly highlighting the potential of combination therapy as an alternative to standard diabetic treatments.